Here we report the design, synthesis and
biological evaluation of surface-modified
silica nanoparticles (SNP) for the delivery of
camptothecin (
CPT).
Drug has been covalently linked to the nanoparticle through an
ester bond with the 20-hydroxy moiety, in order to stabilize its
lactone ring and to avoid unspecific release of the
drug. The obtained material is highly stable in plasma, with low release of the cargo at physiological pH. Cell internalization and in vitro efficacy assays demonstrated that nanoparticles carrying
CPT (SNP-
CPT) entered cells via endocytosis and the intracellular release of the cargo induced cell death with half maximal inhibitory concentration (IC₅₀) values and cell cycle distribution profiles similar to those observed for the naked
drug. Further, in vivo biodistribution, therapeutic efficacy and biocompatibility of the SNP-
CPT were evaluated in human
colorectal cancer xenografts using in vivo fluorescence or bioluminescence optical imaging. In vivo
tumor-accumulation and whole-body tissue distribution were carried out based on the acquisition of fluorescence emission of a fluorophore (
Cy5.5) conjugated to the SNP-
CPT, as well as by HPLC quantification of tissue
CPT levels. The results showed that, although SNP-
CPT tended to accumulate in organs of the reticulo-endothelial system, nanoparticles boost
CPT concentration in
tumor vs administration of the free
drug. Accordingly, SNP-
CPT treatment delayed the growth of subcutaneous
tumors while significantly reducing the systemic toxicity associated with
CPT administration. These results indicate that the SNP-
CPT could be used as a robust drug delivery system for antitumoral treatments based on
CPT.